Revisiting the role of mast cells in autoimmunity

Beside their well known role in allergy, mast cells (MCs) are capable to sense multiple signals and have therefore the potential to be involved in many immune responses. MCs are actively present in the target tissues of some autoimmune disorders, suggesting a possible function in the manifestation of such diseases. This idea is strengthened by the evidence that KIT-dependent MC-deficient mice are protected from disease in many mouse models of autoimmunity, including multiple sclerosis, rheumatoid arthritis and autoimmune skin blistering diseases. Thus, the essential role of MCs in autoimmunity not only significantly extends the knowledge of MCs in the immune response but also provides novel therapeutic targets for the treatment of such diseases. However, recent studies using a new generation of KIT-independent MC-deficient strains could not confirm an essential participation of MCs in autoimmune diseases. Therefore, it is necessary to clarify the observed discrepancies and to elucidate the role of MCs in autoimmune diseases. Here, we review the impact of MCs on the development of autoimmune diseases with focus on the controversial effects of MC deficiency in different mouse models of autoimmune diseases. We also try to clarify contradictory findings in mouse studies to finally elucidate the role of MCs in autoimmunity.